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Details

Stereochemistry ACHIRAL
Molecular Formula C24H23FN4O3
Molecular Weight 434.4628
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OLAPARIB

SMILES

FC1=CC=C(CC2=NNC(=O)C3=C2C=CC=C3)C=C1C(=O)N4CCN(CC4)C(=O)C5CC5

InChI

InChIKey=FDLYAMZZIXQODN-UHFFFAOYSA-N
InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)

HIDE SMILES / InChI
Molecular Formula C24H23FN4O3
Molecular Weight 434.4628
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Olaparib is an oral inhibitor of poly (ADP-ribose) polymerase enzymes, including PARP1, PARP2, and PARP3 which are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has shown activity in ovarian and breast tumors with known BRCA mutations and was the first FDA approved drug in this class. Lynparza (olaparib) is indicated for treatment of gBRCA-mutated advanced ovarian cancer. Its use together with other chemotherapy medicines can lead to increased effects on the blood resulting in reduction in the numbers of white blood cells and platelets, and anaemia.

Originator

Approval Year

2014
86
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7468
Ovarian Neoplasms
Inhibitor
7468
Ovarian Neoplasms
 1.94 nM [IC50]
Inhibitor
7468
Ovarian Neoplasms
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Poly [ADP-ribose] polymerase 3
Poly [ADP-ribose] polymerase 2
Poly [ADP-ribose] polymerase 1
Approved
7883
LYNPARZA
Approved (off-label)
8
PubMed

PubMed

TitleDatePubMed
High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs.
2008 Nov 4
4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1.
2008 Oct 23
Are current drug development programmes realising the full potential of new agents? The scenario.
2009
PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2?
2009
Triple-negative breast cancer: novel therapies and new directions.
2009 Aug 20
Targeting the molecular defect in BRCA-deficient tumors for cancer therapy.
2009 Aug 4
Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.
2009 Jul 9
Preclinical mouse models for BRCA1-associated breast cancer.
2009 Nov 17
Converting cancer mutations into therapeutic opportunities.
2009 Sep
Recent advances in managing triple-negative breast cancers.
2009 Sep 28
Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone.
2010
Present and future evolution of advanced breast cancer therapy.
2010
Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features.
2010
Targeted therapy in ovarian cancer.
2010
Targeted therapies in epithelial ovarian cancer.
2010
A current review of targeted therapeutics for ovarian cancer.
2010
Biology-driven cancer drug development: back to the future.
2010 Apr 12
BRCA mutations in the management of breast cancer: the state of the art.
2010 Dec
Are current development programs realising the full potential of new agents?
2010 Dec 20
ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors.
2010 Feb
PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer.
2010 Feb 11
Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan.
2010 Feb 15
Gateways to clinical trials.
2010 Jan-Feb
[Treatment with oral agents for breast cancer].
2010 Jul
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial.
2010 Jul 24
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial.
2010 Jul 24
Poly(adp-ribose) polymerase inhibitors: a novel drug class with a promising future.
2010 Mar-Apr
Multiple roles of BRIT1/MCPH1 in DNA damage response, DNA repair, and cancer suppression.
2010 May
Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval.
2010 May 20
Does race affect outcomes in triple negative breast cancer?
2010 May 7
Molecule of the month. Olaparib.
2010 Nov
Targeting poly(ADP-ribose) polymerase activity for cancer therapy.
2010 Nov
The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo.
2010 Nov 25
Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699.
2010 Nov 9
Targeted therapies: PARP inhibitor olaparib is safe and effective in patients with BRCA1 and BRCA2 mutations.
2010 Oct
Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.
2010 Oct
New developments in treatment of ovarian carcinoma: focus on trabectedin.
2010 Oct 1
Treatment options for patients with triple-negative breast cancer.
2010 Oct 27
Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype.
2010 Oct 5
Gateways to clinical trials.
2010 Sep
Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil.
2011
5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2).
2011 Apr 14
MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADP-ribose) polymerase inhibitor.
2011 Apr 8
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
2011 Jul
BAP1 loss defines a new class of renal cell carcinoma.
2012 Jun 10
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
2012 Nov 1
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework.
2014 Jun
5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53.
2015 Dec 22
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
2015 Oct 29
Patents

Patents

20080146575
1
20080200469
1
7692006
1
8183369
1
8247416
1

Sample Use Guides

In Vivo Use Guide
400 mg (eight 50 mg capsules) taken twice daily, for a total daily dose of 800 mg. Continue treatment until disease progression or unacceptable toxicity.
Route of Administration: Oral
In Vitro Use Guide
30-100 nM in SW620 cells
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:30:34 UTC 2019
Edited
by admin
on Mon Oct 21 20:30:34 UTC 2019
Record UNII
WOH1JD9AR8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OLAPARIB
DASH   INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
AZD2281
Code English
KEYLYNK-010 COMPONENT OLAPARIB
Code English
OLAPARIB [USAN]
Common Name English
OLAPARIB [WHO-DD]
Common Name English
OLAPARIB [JAN]
Common Name English
AZ2281
Code English
OLAPARIB [VANDF]
Common Name English
KU-0059436
Code English
OLAPARIB [INN]
Common Name English
1(2H)-PHTHALAZINONE, 4-((3-((4-(CYCLOPROPYLCARBONYL)-1-PIPERAZINYL)CARBONYL)-4-FLUOROPHENYL)METHYL)-
Systematic Name English
PIPERAZINE, 1-(CYCLOPROPYLCARBONYL)-4-(5-((3,4-DIHYDRO-4-OXO-1-PHTHALAZINYL)METHYL)-2-FLUOROBENZOYL)-
Systematic Name English
LYNPARZA
Brand Name English
4-((3-((4-(CYCLOPROPYLCARBONYL)PIPERAZIN-1-YL)CARBONYL)-4-FLUOROPHENYL)METHYL)PHTHALAZIN-1(2H)-ONE
Systematic Name English
AZD-2281
Code English
OLAPARIB [MI]
Common Name English
KU-59436
Code English
OLAPARIB COMPONENT OF KEYLYNK-010
Code English
OLAPARIB [MART.]
Common Name English
AZ-2281
Code English
Classification Tree Code System Code
NDF-RT N0000191623
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
EMA ASSESSMENT REPORTS LYNPARZA (AUTHORIZED: OVARIAN NEOPLASMS)
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
FDA ORPHAN DRUG 417613
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
EU-Orphan Drug EU/3/07/501
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
FDA ORPHAN DRUG 409213
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
WHO-ATC L01XX46
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
FDA ORPHAN DRUG 655318
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
NCI_THESAURUS C62554
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
FDA ORPHAN DRUG 419013
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
Code System Code Type Description
EVMPD
SUB32234
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
MERCK INDEX
M8185
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY Merck Index
ChEMBL
CHEMBL521686
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
NCI_THESAURUS
C71721
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
INN
8685
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
RXCUI
1597582
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY RxNorm
IUPHAR
7519
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
CAS
763113-22-0
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
PUBCHEM
23725625
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
DRUG BANK
DB09074
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
MESH
C531550
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
WIKIPEDIA
OLAPARIB
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY
NDF-RT
N0000191622
Created by admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
PRIMARY Poly(ADP-Ribose) Polymerase Inhibitors [MoA]
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
Structure of OLAPARIB
EXCRETED UNCHANGED
FECAL
MATE-2
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
The clinical relevance of these findings is unknown.
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
POLY (ADP-RIBOSE) POLYMERASE 1
TARGET -> INHIBITOR
DT40 cells cytotoxicity
BINDING
IC50
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
OAT-3
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
OATP1B1
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
Structure of OLAPARIB
EXCRETED UNCHANGED
URINE
OCT-2
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
Inhibitor at higher concentrations than are clinically achieved.
MINOR
OCT-1
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
Related Record Type Details
Structure of OLAPARIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
NIH
NCATS
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